The goal of this project is to understand the genetic mechanisms underlying the robust preference of the Dengue Fever Mosquito for human scent. The proposed research promises to (1) provide insight into the molecular basis of olfactory behavior and (2) provide specific information useful for preventing the spread of human disease by mosquitoes. The experimental plan leverages the power of a comparison between natural mosquito populations that exhibit a striking difference in olfactory preference. An ancestral, forest form of the Dengue Fever Mosquito prefers the odor of non-human animals, while a recently evolved, domestic form strongly prefers human odor. The first (mentored) part of the project will compare the antennal, maxillary palp, and brain transcriptomes of these two forms to generate a list of candidate genes that may regulate preference. The second (mentored) part of the project will compare odor-evoked neurophysiological activity in the first processing center of the brain to pinpoint differences in host odor representation and generate hypotheses about how the candidates act through olfactory signaling cascades to alter behavior. The third (independent) part of the project will use a combination of functional and transgenic studies to test the specific hypothesis that changes in the sequence and/or pattern of expression of candidate chemoreceptors and other olfactory genes are essential for human host preference. The results are expected to provide insight into the way olfactory preferences are determined and will focus efforts to develop novel approaches to prevent mosquitoes from biting humans and transmitting human disease. PUBLIC HEALTH RELEVANCE: A keen sense of smell helps insects find and spread disease to hundreds of millions of people each year. The most deadly insect vectors of human disease are preferentially attracted to human scent over that of other animals. This project is designed to reveal the molecular basis of mosquito olfactory preference for human scent and could be useful for developing new ways to prevent insects from biting humans.